Cope rearrangement product aromatization

Thomas and Ozainne have explored the tandem Qaisen-Cope rearrangement on aromatic substrates. Treatment of 2-furfuryl alcohol with diene (25 equation 9) provides a 9 1 mixture of Claisen-Cope product (39) and furan (37), respectively. The minor component arises via the forbidden [1,3] prototropic shift of the initial Claisen intermediate (38), thereby reestablishing the aromaticity of the furan ring. 

Pd2(dba)3/l,4-bis(diphenylphosphino)butane (DPPB) in the presence of 2-mercaptobenzoic acid <95TL1267>. The Af-allylindolines can be easily oxidized to the corresponding indoles at room temperature with o-chloranil. Additionally, Al-allylanilines were also found to undergo aromatic 3-aza-Cope rearrangements in the presence of Zeolite catalysts to give indoline derivatives as the major product <96TL5281>. 

The reaction with the siloxy derivative 29 is an interesting example because the product 30 is a 1,5-dicarbonyl derivative (Equation (36)).96 1,5-Dicarbonyls are classically prepared by a Michael addition, but the synthesis of 30 by a Michael addition is not possible because it would require addition to the keto form of 1-naphthol. The acetoxy derivative 31 resulted in a different outcome, leading to the direct synthesis of the naphthalene derivative 32 (Equation (37)).96 In this case, the combined C-H activation/Cope rearrangement intermediate was aromatized by elimination of acetic acid before undergoing a reverse Cope rearrangement. 

The Cope rearrangement mechanism can be also strongly affected by other substituents. Thus, the normal electrocyclic process in the thermal isomerization of divinyl aromatics has been suppressed relative to the thermolysis of l,2-bis(trifluorovinyl)naphthalene 438 (in benzene, at 193 °C, 24 h)231. Three major products 440-442 were isolated from the reaction mixture, but none of them was the expected product 439. Also formed in low... 

We used the all-carbon Cope rearrangement 29 to introduce this section but now we want to feature the more useful Claisen rearrangements.14 The aliphatic Claisen 54 works for most substituents because an alkene is lost and a much more stable carbonyl group is formed 55. It doesn t matter whether we have an aldehyde (X = H), a ketone, (X = R), an acid (X — OH), an ester (X = OR) or an amide (X = NR2), the reaction works well. The original Claisen rearrangement was the aromatic version 56 that gives an unstable non-aromatic intermediate 57 that quickly loses a proton to restore the aromatic ring and the product is a phenol 58. 

An interesting example of the transfer of center chirality to helicity is the work by Ogawa et al., based on an asymmetric aromatic oxy-Cope rearrangement to provide nonracemic [5]helicenes (Fig. 15.8) [75]. The starting material with center chirality, bicyclo[2,2,2]ketone (-)-21 (>98% ee), was obtained by enzymatic resolution. In the annelation step, the phenanthrene derivative was subjected to aromatic oxy-Cope rearrangement, to afford a pentacyclic product in 47 % yield. The corresponding [5]helicene 22 was obtained in 7 % overall yield (> 98 % ee) after six steps. 

The implication of the multiple possible reaction pathways shown in Scheme 4.6 is that any computational approach must allow for the possible contribution of at least these three valence bond structures. " The simplest approach to the nature of the wavefunction for the Cope rearrangement is to just account for the correlation of the active orbitals of the reactants with those of the products. The o-bond between C3 and C4 of the reactant correlates to a(Ci-C ) in the product. Assuming that 1,5-hexadiene has C2 symmetry, both of these orbitals have a synunetry. The in-phase mixing of the two jc-bonds of the reactant (it(Cx-C2)-l-Jc(C5-Cg)) has b synunetry and correlates with (jc(C2-C3)-l-Jt(C4-C5)) of the product. The out-of-phase combination of the reactant Jc-bonds (it(Ci-C2) - it(C5-Cg)) has a synunetry and correlates with (jc(C2-C3) - Jc(C4-C5)) of the product. If the reaction proceeds through a C211 geometry, orbital symmetry demands that these active orbitals of must become Ug aJbJ. So, we may take as the aromatic ... 

A second example of this tandem reaction sequence was in the synthesis of 4-aryl-4-(l-naphthyl)-2-butenoates 174 (Scheme 42, right) [113, 117]. As in the indole synthesis, an acetoxy group was lost following the C-H activation/ Cope rearrangement, providing the aromatized products. Thirteen examples of this transformation were provided, with yields ranging from 45 to 92%, and enantioselectivities all >98%. 

Instead of dienes, aromatic substrates can also participate in tandem cyclopropanation/Cope rearrangement sequences893 894. Rhodium(II) trifluoroacetate catalyzed decomposition of 17 affords the unstable bicyclo[3.2.2] compound 149 in 29% yield893. The reactions of anisol and 1-methoxynaphthalene with 17 show that in the case of electron-rich aromatics side reactions (alkylation reactions) can compete with cyclopropanation reactions due to dipolar intermediates and products 150 and 151, respectively, are formed893. 

Addition of carbenes to aromatic systems leads to ring-expanded products. Methylene itself, formed by photolysis of diazomethane, adds to benzene to form cycloheptatriene in 32% yield a small amount of toluene is also formed by an insertion reaction. The cycloheptatriene is formed by a Cope rearrangement of the intermediate cyclopropane (a norcaradiene). More satisfactory is the reaction of benzene with diazomethane in the presence of copper salts, such as copper(I) chloride, which gives cycloheptatriene in 85% yield (4.87). The reaction is general for aromatic systems, substituted benzenes giving mixtures of the corresponding substituted cycloheptatrienes. 

The first step is a Cope rearrangement—a [3,3]-sigmatropic rearrangement made favourable in this case because the a-bond that is broken is in a three-membered ring. The product cannot go directly to an aromatic compound as that would require a [1,3] (or a [1,7] depending on how you count) hydrogen shift. Such a shift would have to be antarafacial on the 3i-system and that is impossible in such a rigid structure. 

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